Cytokines are soluble molecules that have an important role important role in the development and function of essentially all cells which comprise the immune system. Two cytokines i paticular, interleukin-12 (IL-12) and IL-4, are importnat for the differentiation of subsets of T helper(Th) cells known as Th1 and Th2 cells, respectively. For a large number of diseases, the types of cytokines produced, and therefore the subsets of Th cell generated, often dictates that severity of the disease and the clinical outcome. The overall goal of this proposal is to begin to identify the molecular mechanisms by which cytokines such as IL-4 elicit specific immune responses involving distinct subsets ofTh cells. While it has been well appreciated that the binding of cytokines to their cell surgace receptors induces the transcription of new gene programs, there recent identification of a novel class of latent transcriptional facotrs, known as a signal transducer and activator of transcription. Experiments outlined in this proposal examine several aspects of the differentiation and function of Th2 cells, including th erole of CD1-restricted CD4=NK1.1= T cells as the physiologic source of IL-4 necessary for the generation of the Th2 cells, the molecular mechanisms by which STAT proteins mediate the differentiation of Th2 cells and the role of TH2 cells in murine models of inflammation and autoimmunity.